Atrial fibrillation (AF) is one of the most common arrhythmias in the elderly. In many cases AF is associated with underlying cardiovascular pathology, but AF can also occur in aged individuals with otherwise normal hearts. This suggests that age-dependent modifications of atrial function can cause AF. In preliminary experiments we have established that aged (24 month old) mice are more prone to pacing-induced AF than young mice. As in ventricular myocytes, a rise in intracellular Ca2+ triggers atrial myocyte contraction. While the role of alterations in intracellular Ca2+ in the generation of ventricular arrhythmias has been demonstrated, the impact of altered Ca2+ handling in the genesis of AF has not been firmly established. The central hypothesis of this fellowship application is that alterations in atrial myocyte Ca2+ handling contribute to AF in aging hearts. Specifically, we aim to demonstrate that pathologic diastolic SR Ca2+ release (leak) is a contributing factor in AF and that repairing this dysfunction will provide therapeutic strategies for treating AF in humans.